An androgen-dependent condition, disease, disorder, or syndrome, is a medical condition that is, in part or full, dependent on, or is sensitive to, the presence of androgenic activity in the body. Known androgen-dependent conditions include acne, seborrhea, androgenic alopecia, telogen effluvium and hidradenitis suppurativa.
Hair loss, also known as alopecia or baldness, refers to a loss of hair from the head or body. Baldness can refer to general hair loss or male pattern hair loss. Male-pattern baldness or androgenetic alopecia accounts for more than 95% of hair thinning in adult men. Androgen-dependent disorders in general and specifically androgenetic alopecia have been correlated with increased levels of androgenic hormones in the roots of the hair follicle. Androgenic hormones reported to be over-produced in androgenic alopecia include dihydrotestosterone (DHT), a derivative of testosterone, or 5α-dihydrotestosterone (5α-DHT), also known as androstanolone (5α-androstan-17β-ol-3-one) as well as 17β-hydroxy-5α-androstan-3-one, a sex steroid and androgen hormone. The enzyme 5α-reductase synthesizes DHT in the prostate, testes, hair follicles, and adrenal glands. This enzyme reduces the 4,5 double-bond of the hormone testosterone. It is believed that the accumulation of androgenic hormones in the roots of the hair follicle leads to blockage of blood flow, reduced oxygen supply, and subsequent thinning of the hair.
B. subtilis is a gram-positive, rod-shaped bacterium found on skin, in the digestive tract, in epithelial wounds, on extremities of the human body including the human scalp. The strain is commercially used as a skincare product, a food ingredient for human consumption, in animal feed, in fertilizer, and in an antibiotic substitute. B. subtilis has several secretion systems, consisting of elements responsible of detection, transport and folding of secreted proteins. A common way to induce the secretion of a heterologous protein is via the addition of a naturally occurring signal peptide. Consequently, the widespread use of B. subtilis indicates its low-risk usability in commercial products, while its prevalence on the human scalp facilitates a pathway for microbiome engineering.
Inhibitors of 5α-reductase have been disclosed in U.S. Pat. Nos. 6,380,179 9,144,560 such as for alopecia. U.S. Pat. No. 6,710,037 discloses administration of 3α-HSD for the treatment of androgen-dependent disorders. An amino acid sequence of 3α-HSD and a pseudomonas aeruginosa 3α-HSD gene sequence, are disclosed in CN10090688 and CN2014/10591668, respectively.
There is an unmet need for novel therapies for treating androgen-dependent disorders, which are safe and have little or no side effects.